Evaluation of Physical and Chemical Changes in Pharmaceuticals Flown on Space Missions
Evaluation of Physical and Chemical Changes in Pharmaceuticals Flown on Space Missions
复制标题
DOI：
10.1208/s12248-011-9270-0
复制
发表时间：
2011-06-01
期刊：
影响因子：
4.5
通讯作者：
Putcha, Lakshmi
中科院分区：
文献类型：
--
作者：
Du, Brian;Daniels, Vernie R.;Putcha, Lakshmi
用于治疗太空宇航员的药物的有效性和安全性可能会因太空稳定性的改变而受到影响。我们比较了存放在国际空间站(ISS)和地球上的相同药盒中包含的35种配方中的物理和化学变化与时间的关系。有效药物含量(API)返回地球后用超高效液相色谱仪测定。在太空存放28个月后，国际空间站上的6种药物和地面对照的2种药物显示出物理变量的变化；来自国际空间站的9种药物和地面的17种药物在储存28个月后符合美国药典(USP)对原料药含量的接受标准。来自每个飞行套件的较高比例的药物的原料药含量低于各自的地面控制组。不符合原料药要求的药物数量在空间上作为时间的函数而增加，与有效期无关。许多药物在太空中的降解速度比在地面上更快，大多数固体剂型在太空储存后符合USP的溶出度标准。在空间中，累积辐射剂量较高，且随时间增加，而温度和湿度与地面相似。在航天器上暴露于长期低剂量的电离辐射，以及在飞行专用分配器中重新包装固体剂型，都可能对药物的稳定性产生不利影响。描述不稳定配方的降解情况，并确定地球上空间模拟环境中稳定性的化学属性，将有助于开发空间耐寒药物。
Efficacy and safety of medications used for the treatment of astronauts in space may be compromised by altered stability in space. We compared physical and chemical changes with time in 35 formulations contained in identical pharmaceutical kits stowed on the International Space Station (ISS) and on Earth. Active pharmaceutical content (API) was determined by ultra- and high-performance liquid chromatography after returning to Earth. After stowage for 28 months in space, six medications aboard the ISS and two of matching ground controls exhibited changes in physical variables; nine medications from the ISS and 17 from the ground met the United States Pharmacopeia (USP) acceptance criteria for API content after 28 months of storage. A higher percentage of medications from each flight kit had lower API content than the respective ground controls. The number of medications failing API requirement increased as a function of time in space, independent of expiration date. The rate of degradation was faster in space than on the ground for many of the medications, and most solid dosage forms met USP standard for dissolution after storage in space. Cumulative radiation dose was higher and increased with time in space, whereas temperature and humidity remained similar to those on the ground. Exposure to the chronic low dose of ionizing radiation aboard the spacecraft as well as repackaging of solid dosage forms in flight-specific dispensers may adversely affect stability of pharmaceuticals. Characterization of degradation profiles of unstable formulations and identification of chemical attributes of stability in space analog environments on Earth will facilitate development of space-hardy medications.